The U19 Sexually Transmitted Infections Cooperative Research Center (STI CRC), ?University of North Carolina - Chlamydia Vaccine Initiative (UNC-CVI)? brings together a synergistic multidisciplinary group of project leaders/principal investigators (PI) with clinical and basic research expertise in STI research and a history of effective collaboration, to support a vaccine development pipeline comprising vaccine antigen assessment, vaccine testing in animal models, and identification of human correlates of efficacy. The UNC-CVI STI CRC will accomplish our goal through three projects. Project 1, Human Responses to Candidate Chlamydial Antigens (Darville, Goonetilleke, Co-PIs) will exploit responses of women highly exposed to CT to identify candidate vaccine antigens through profiling of CD4 and CD8 responses. Project 2, Chlamydial Vaccine Testing in Mice and Guinea Pigs (Beagley and Goonetilleke, Co-PIs) will explore the efficacy of two leading T cell vaccine modalities already proven safe and effective in humans, as a route to establishing lasting immunity to chlamydial challenge in mice and guinea pigs. We have enlisted collaborative experts at The Jenner Institute who will advise and generate replication-incompetent viral vectors expressing chlamydial immunogens for use in a heterologous prime-boost strategy, and experts at BlueWillow Biologics who will advise and manufacture recombinant chlamydial immunogens in nanoemulsion, Nanovax? for use as intranasal vaccines. Finally, Project 3, Biomarkers of Chlamydial Susceptibility and Disease (O?Connell and Zheng, Co-PIs) addresses a critical need for biomarkers to accelerate rational vaccine design and testing, by supporting identification of individuals most likely to benefit from immunization, enabling balanced group recruitment for vaccine trials and serving as surrogate endpoints. These projects will be supported by an Administrative Core and a Clinical Core. The Administrative Core will serve as the Center?s communications hub and will provide administrative and scientific oversight of Center functions, including a Developmental Research Program (DRP) that will foster new investigators in STI vaccine research, and a Biostatistical Support Group that will serve all projects and DRP awardees. The Clinical Core will identify and enroll women with or at-risk for STI and collect clinical specimens required to complete the projects. These investigators, projects and cores represent a unique combination of skills and experience to address a significant public health problem. Upon completion of this program, we anticipate having identified novel chlamydial vaccines with a highly feasible path to clinical testing and licensure.